Comparison of Fixed Dose Combination Perindopril/Amlodipin Influence on Target Organ Damage in Patients with Hypertension and Ischemic Heart Disease and without It (Results of EPHES Study)

Abstract

EPHES trial (Evaluation of influence of fixed dose combination Рerindopril/amlodipine on target organ damage in patients with arterial HypErtension with or without iSche­mic heart disease) had aim to compare the effect of fixed-dose combination (FDC) perindopril/amlodipine on blood pressure (BP) decrease and the dynamics of target organ damage patterns in patients with arterial hypertension (AH) with and without ischemic heart disease (IHD). Materials and methods. EPHES study included 60 patients aged over 30 years with AH: the first group — 30 individuals without IHD, the second one — 30 persons with IHD. The follow-up period was 12 months. All patients in the day of randomization were administered FDC perindopril/amlodipine in baseline dose 5/5 mg once a day. If it was necessary (BP > 140/90 mmHg), the doses of FDC components were increased gradually every two weeks to 10/10 mg, and after 6 weeks of treatment, indapamide 1.5 mg was added. 66.7 and 96.7 % of patients from the first and second groups received beta-blockers. All patients underwent the measurement: of body weight and height, office levels of systolic BP (SBP), diastolic BP (DBP) and heart rate (HR), ambulatory BP, pulse wave velocity in elastic (PWVe) and muscle arteries, central SBP, augmentation index adjusted to HR 75 bpm (Aix75), biochemical blood count, echocardiography, echocardiography with Doppler, ankle-brachial index, intima-media thickness. Results. It was found that prescribed therapy based on FDC perindopril/amlodipine, regardless of the presence or absence of IHD, has reduced the office, average daily, daytime, night-time and central BP effectively (to target levels) and safely. At the same time, initially increased day and night BP variability, the value of morning rise of SBP and proportion of patients with circadian non-dipper BP profile have significantly decreased, but these figures were cinsiderably higher in patients with IHD at all stages of treatment. Patients with IHD and without it have no differences in the initial value of АІх75, and against the background of prescribed therapy, there was a significant decrease of this index in both groups, but in patients with IHD this reduction of АІх75 was significantly lower than in the group without IHD that probably was due to more frequent use of beta-blockers. Treatment, effective in terms of reducing BP, has led in both groups to a significant decrease of target organ dama­ge — improving the elastic properties of the aorta and left ventricular diastolic function, reduction in the level of albuminuria, in left ventricular hypertrophy and left atrial size. The degree of PWVe decrease was significantly (P < 0.005) lower in patients without IHD than in the group with IHD — 2.5 ± 0.2 m/s vs 4.4 ± 0.5 m/s. In addition, despite the same degree of reduction in the left ventricular mass, an improvement of left ventricular diastolic function (increased E/A and reduced E/E’) was higher in the group of patients with IHD — by 64.4 and 54.1 % against 39.8 and 23.2 %, respectively (P < 0.05 for both indicators). The maximum value of intima-media thickness has significantly decreased only in patients with IHD. The therapy did not lead to significant changes in biochemical parameters and was well tolerated by patients — adverse events reported in 2 (6.5 %) persons in the group without IHD and in 3 (10 %) patients in the group with IHD (P = NS between groups). The groups did not differ significantly by the dynamics of complaints, and patients with IHD, who had angina at baseline, had a significant decrease in the number of angina attacks per week — from 2.5 ± 0.4 to 1.2 ± 0.2 (P < 0.01). Conclusions. Thus, treatment of AH based on FDC perindopril/amlodipine was effective in reducing BP and regression of target organ damage, regardless of the presence of IHD. Chan­ges of the indicators characterizing the target organ damage were somewhat different in patients with and without IHD that must be considered, when choosing treatment regimen.

2013 ESH/ESC Guidelines for the management of arterial hypertension. The Task Force for the management of arte­rial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // Journal of Hypertension. — 2013. — Vol. 31. — P. 1281-1357.